Since February 2022, the war in Ukraine has led to large-scale displacement, including people living with HIV (PLWH). Early reports described predominantly virologically suppressed individuals with preserved immune funct...Since February 2022, the war in Ukraine has led to large-scale displacement, including people living with HIV (PLWH). Early reports described predominantly virologically suppressed individuals with preserved immune function. Data on refugees with HIV presenting during later phases of the war are limited. We conducted a retrospective single-center study including adult refugees with HIV from Ukraine presenting to a tertiary care center in Germany. Paticipants were grouped by time of presentation: Cohort 1 (March-December 2022) and Cohort 2 (January 2023-February 2024). Clinical, immunological, and virological parameters were compared between cohorts. A total of 86 individuals were included (Cohort 1: n = 46; Cohort 2: n = 40). Participants in cohort 2 more frequently received their first HIV diagnosis after presentation in Germany, with no previously documented HIV diagnosis in Ukraine or elsewhere, compared with cohort 1 (67% vs. 5%; p < 0.0001). Participants in Cohort 2 more often presented with detectable HIV RNA (65% vs. 29%; p < 0.0001) and advanced immunodeficiency (CD4 < 200/µL: 28% vs. 9%; p < 0.05). Among individuals with prior HIV diagnosis, virological failure was more common in Cohort 2 (50% vs. 14%; p = 0.006). AIDS-defining illnesses occurred more frequently in Cohort 2 (p = 0.005). Serological evidence of HBV and HCV infection was high in both cohorts. Refugees with HIV from Ukraine presenting during later phases of the war exhibit more advanced disease and poorer virological control compared with earlier arrivals. These findings suggest increasing disruption of HIV care over time and highlight the need for low-threshold access to testing, comprehensive screening, and rapid initiation of antiretroviral therapy in this population.
Romani P, Nirchio N, Arboit M
… +20 more, Barbieri V, Tosi A, Michielin F, Shibuya S, Benoist T, Wu D, Hindmarch CCT, Giomo M, Urciuolo A, Giamogante F, Roveri A, Chakravarty P, Montagner M, Calì T, Elvassore N, Archer SL, De Coppi P, Rosato A, Martello G, Dupont S
Bang YH, Kang D, Lee S
… +22 more, Kim S, Jeon I, Park E, Choi J, Song GW, Yoo MW, Song JS, Song IH, Kim YH, Kim HR, Song HJ, Kim DH, Choi KD, Lee JH, Ahn JY, Shim JH, Lee D, Choi J, Kim JE, Kim SY, Bae DJ, Park SR
Neoadjuvant immunotherapy may improve long-term outcomes by activating antitumor immunity before surgery. We evaluated danburstotug (IMC-001), an anti-PD-L1 antibody, in resectable gastric cancer (GC), esophageal squamou...Neoadjuvant immunotherapy may improve long-term outcomes by activating antitumor immunity before surgery. We evaluated danburstotug (IMC-001), an anti-PD-L1 antibody, in resectable gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), and hepatocellular carcinoma (HCC). In this phase II trial, patients received two cycles of danburstotug (20 mg/kg every 2 weeks) before surgery. The primary endpoint was major pathologic response (MPR, <10% viable tumor). Key secondary endpoints included safety, radiologic/metabolic response, survival outcomes, and translational immune profiling. Forty-eight patients were evaluable (16 per cohort). The study did not meet its pre-specified primary endpoint, with MPR achieved in 2/48 patients (4.2%)-one ESCC and one HCC (6.3% per cohort). However, pathologic tumor regression to ≤50% viable tumor was observed in 11/48 patients (22.9%; GC 25.0%, ESCC 31.3%, HCC 12.5%). Among evaluable patients, partial responses were observed radiographically in 17.6% and metabolically in 23.3%. Treatment was well tolerated, with grade ≥3 treatment-related adverse events in 6.0% and no grade 4-5 events; two surgical delays were observed, of which one was treatment-related. All patients underwent surgery with R0 resection. Immune profiling revealed cancer type-specific immune-remodeling. Neoadjuvant danburstotug was safe, did not compromise surgical outcomes, and provided exploratory insights into treatment-induced immune microenvironment remodeling. ClinicalTrials.gov ID: NCT04196465, date of registration: August 28, 2019.
Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipid...Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy metabolism compared to young adults with comparable activity levels. Here we found that 50% of these age-related differences were absent in trained older adults, resulting in profiles resembling those of young adults. Although all participants displayed transcriptional immune and stress responses upon acute exercise, the magnitude of these responses in older adults was positively correlated with their physical fitness. Integrated multiomic analyses further revealed links among mitochondrial respiration, lipid metabolism, stress responses and NAD biology. These findings demonstrate that sustained physical training transforms age-related molecular profiles and provide a molecular atlas for study of fitness-dependent aging mechanisms.
Automated segmentation of PDAC is a prerequisite to realize the promise of precision oncology, yet existing approaches remain insufficiently validated at the cohort scale and acquisition heterogeneity required for clinic...Automated segmentation of PDAC is a prerequisite to realize the promise of precision oncology, yet existing approaches remain insufficiently validated at the cohort scale and acquisition heterogeneity required for clinical deployment. We developed and validated a pancreas-localized three-dimensional convolutional neural network model (Model-BB) using 1859 multi-institutional treatment-naïve, biopsy-confirmed PDAC CT examinations. Model-BB achieved a DSC of 0.76 ± 0.13 on internal testing and 0.76 ± 0.09 on external validation, with stable performance across acquisition site, scanner vendor, slice thickness, and temporal epochs. Upstream localization analysis showed complete tumor enclosure in 224 of 241 test cases (92.9%), with preserved performance (DSC 0.78) among cases with partial peripheral exclusion, indicating that localization error was not the principal source of reduced performance. In a controlled architectural benchmark, Model-BB outperformed Swin UNETR, a 3D vision transformer (DSC, 0.76 ± 0.13 versus 0.68 ± 0.18; p < 0.001). On a difficulty-enriched subset (n = 50), Model-BB achieved DSC 0.71 against a STAPLE-derived consensus, exceeding individual reader-pair agreement (DSC range, 0.57-0.65), with concordance correlation coefficient 0.93 for tumor volume. These findings support anatomically constrained, task-specific segmentation as a reproducible geometric substrate for volumetric tumor-burden quantification, treatment-response assessment, and multimodal outcomes modeling, pending prospective validation in clinical-trial workflows.
Salmonella enterica remains a leading foodborne zoonotic pathogen worldwide, with poultry serving as a major reservoir and vehicle for antimicrobial resistance dissemination to humans. This study investigated the genotyp...Salmonella enterica remains a leading foodborne zoonotic pathogen worldwide, with poultry serving as a major reservoir and vehicle for antimicrobial resistance dissemination to humans. This study investigated the genotypic basis and distribution of multidrug resistance (MDR) among 29 S. enterica isolates from broiler farms in Egypt, emphasizing the role of mobile genetic elements as integrons and the assessment of genetic relatedness using ERIC-PCR. Molecular screening revealed high prevalence of resistance determinants, including floR (93.1%), tetA (86.2%), aphA1 (82.8%), cmlA (75.9%), ereA (75.9%), sulI (62.1%), aadA1 (51.7%), dfrA1 (48.3%), aac(3)-IV (44.8%), tetB (41.4%), sulII (31.0%), aac(6')-Ib-cr (24.1%), catA1 (20.7%), fosA3 (20.7%), and qnrA (10.3%). High-risk serovars, including S. Jerusalem, S. Colorado, and S. Kentucky, harbored multiple resistance genes and exhibited pronounced XDR profiles. Notably, this study reports the detection of aphA1 and fosA3 in Salmonella isolates derived from broiler chickens, which may represent an early or uncommon finding in Egypt. Many resistance genes were associated with horizontally transferable class 1 integron, underscoring its key role in the dissemination of multidrug resistance (MDR) within poultry systems and along the food chain. ERIC-PCR genotyping segregated isolates into two major genetic groups with seven sub-clusters, reflecting clustering patterns and genetic diversity among the isolates, alongside notable heterogeneity in resistance, virulence, and biofilm-associated genes.Overall, poultry in Egypt represents a significant reservoir of genetically diverse and potentially transmissible MDR S. enterica, highlighting the need for enhanced antimicrobial stewardship and genomic surveillance to mitigate public health risks.
Hiroki S, Fukasawa T, Honda M
… +1 more, Kawakami K
Pharmacoepidemiol Drug Saf
· 2026 Jul · PMID 42399205
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PURPOSE: Observational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, a...PURPOSE: Observational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, and use of total cancer as a composite outcome, which precludes adequate adjustment for site-specific confounding. These limitations can be mitigated by explicitly emulating a target trial with a suitable active comparator. METHODS: We emulated a target trial using a Japanese claims database (April 2014-March 2024) to assess whether metformin reduces colorectal cancer (CRC) risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. DPP-4is served as an active comparator because they are widely used as first-line alternatives in Japan and have no clear evidence of affecting CRC risk. We estimated the observational analogue of the per-protocol effect using pooled logistic regression with inverse probability weighting to adjust for baseline and time-varying confounders. RESULTS: Among 26 273 metformin users and 108 299 DPP-4i users, the 5-year risk of CRC was 1.55% (95% confidence interval, 1.16 to 2.04) versus 1.26% (1.13 to 1.41), yielding a risk difference of 0.29% (-0.12 to 0.79) and a risk ratio of 1.23 (0.91 to 1.66). CONCLUSIONS: Metformin use did not reduce the 5-year risk of CRC compared with DPP-4is. This finding is consistent with meta-analyses of randomized trials and contrasts with earlier observational reports of substantial benefit, which were likely inflated by methodological flaws. Explicitly emulating a target trial minimized design-related biases and provided estimates that support causal interpretation.
Ohashi Y, Maruta A, Koizumi T
… +12 more, Iwata S, Uemura S, Tezuka R, Iwasa Y, Okuno M, Iwata K, Mukai T, Ichikawa H, Mita N, Yoshida K, Iwashita T, Shimizu M
Pancreatology
· 2026 Jun · PMID 42399187
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BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a well-recognized precursor of pancreatic cancer; however, the optimal surveillance strategy for IPMN remains controversial. This study aimed to evaluate the...BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a well-recognized precursor of pancreatic cancer; however, the optimal surveillance strategy for IPMN remains controversial. This study aimed to evaluate the clinical impact of semiannual surveillance using endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) for the detection of malignant transformation, including IPMN-derived and concomitant carcinoma. METHODS: This multicenter prospective observational study included 360 patients with branch-duct or mixed-type IPMN enrolled between April 2018 and December 2025. Patients underwent surveillance every 6 months with blood tests and EUS or MRI. The primary endpoint was the curative resection rate among patients diagnosed with IPMN-derived or concomitant carcinoma. Secondary endpoints included the incidence of newly developed worrisome features (WF) and high-risk stigmata (HRS), as well as the cumulative incidence of malignancy. RESULTS: During a median follow-up period of 69 months, newly developed WF and HRS were observed in 30.3% and 2.5% of patients, respectively. Malignant transformation was confirmed in 12 patients (3.3%), including nine with IPMN-concomitant carcinoma and three with IPMN-derived carcinoma. Curative resection was performed in 9 of these patients, resulting in a surgical transition rate of 75.0%. All malignant pancreatic lesions were detected at a resectable or borderline-resectable stage at diagnosis. CONCLUSIONS: Semiannual surveillance using EUS and MRI facilitated the detection of malignant pancreatic lesions at a surgically treatable stage in patients with IPMN. This surveillance strategy may be clinically valuable for identifying IPMN-derived and concomitant carcinoma at stages amenable to surgical treatment in high-risk populations.
OBJECTIVES: The primary focus of this study was to compare the diagnostic accuracy of temporal muscle (TM) B-mode ultrasound and shear wave elastography (SWE) parameters in the assessment of pediatric and to establish pr...OBJECTIVES: The primary focus of this study was to compare the diagnostic accuracy of temporal muscle (TM) B-mode ultrasound and shear wave elastography (SWE) parameters in the assessment of pediatric and to establish practical cutoff values for clinical use. METHODS: This prospective observational study included a total of 89 children aged 5-18 years, consisting of 35 primary malnourished patients and 54 healthy controls. TM thickness, total tissue thickness (muscle and subcutaneous fat), tissue stiffness, and shear wave speed were measured in the temporal fossae using a high-frequency linear transducer. For SWE quality standardization, Motion Stability (M-STB) and Reliability (RLB) indices were actively utilized. The obtained data were modeled using multivariate logistic regression, Decision Curve Analysis (DCA), and receiver operating characteristic (ROC) curves. RESULTS: All investigated ultrasonographic and biomechanical values were significantly lower in the malnutrition group compared to controls (p < 0.001). In the multivariate logistic regression analysis, which was adjusted to resolve multicollinearity (VIF > 20) among the SWE parameters, TM thickness emerged as the strongest independent predictor of malnutrition (OR = 0.428, p < 0.001). ROC analyses demonstrated that TM thickness yielded the highest diagnostic accuracy (AUC = 0.887). A cut-off value of approximately 11.15 mm for this parameter provided a sensitivity of 82.9% and specificity of 90.7%. The DeLong test results confirmed that the discriminatory power of TM thickness was statistically superior to that of the elastography data. CONCLUSIONS: TM thickness measurement via B-mode ultrasound is a practical, reproducible, and promising adjunctive point-of-care parameter for detecting malnutrition-induced muscle atrophy in pediatric patients, demonstrating superiority over SWE parameters; however, external multicenter validation is warranted before routine clinical implementation.
Xiang YJ, Liu ZH, Feng JK
… +49 more, Qin YY, Yu HM, Cheng YQ, Chen G, Wu JY, Zeng YY, Tang YF, Rao JH, Zhang FM, Yang SY, Wang GR, Ye LS, Lang R, Lin JH, Zheng YT, Mao YF, Zhou HK, Yan ML, Liang C, Ren SS, Wang K, Gong L, Xu S, Xu YF, Ni QQ, Wang K, Fan RF, Hu YL, Jiang T, Lin C, Gao QL, Wang ZQ, Lu YM, Zou WB, Wang X, Feng C, Wang ZC, Liu PJ, Wei WJ, Zhang F, Wu W, Lu HF, Huang JY, Liang X, Li JJ, Shan YF, Zhang XP, Cheng SQ, Chinese Association of Liver Cancer and Chinese Medical Doctor Association
BACKGROUND: Recurrence after curative-intent resection remains common in hepatocellular carcinoma (HCC), and whether postoperative incretin-based treatment choice influences outcomes in patients with type 2 diabetes (T2D...BACKGROUND: Recurrence after curative-intent resection remains common in hepatocellular carcinoma (HCC), and whether postoperative incretin-based treatment choice influences outcomes in patients with type 2 diabetes (T2D) is unclear. OBJECTIVE: To determine whether postoperative initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs), compared with dipeptidyl peptidase-4 inhibitors (DPP-4is), is associated with improved recurrence-free and overall survival after curative-intent resection for HCC. DESIGN: Active-comparator, new-user target trial emulation using electronic medical records from 36 hospitals across China from 2014 to 2023, with follow-up through 1 October 2025. Eligible adults had histologically confirmed HCC and T2D, underwent R0 resection and initiated a GLP-1RA or DPP-4i within postoperative days 0 to 90. Time zero was the first qualifying prescription or order date. The primary estimand was intention-to-treat; a prespecified per-protocol analysis assessed sustained adherence. The primary outcome was recurrence-free survival (RFS), treating death without recurrence as a competing event; overall survival (OS) was secondary. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2600118495). RESULTS: Among 42 855 patients with HCC and T2D who underwent liver resection, 1249 were included in the final analytical cohort, including 723 DPP-4i initiators and 526 GLP-1RA initiators; median follow-up was 50.8 months. In weighted intention-to-treat analyses, GLP-1RA versus DPP-4i initiation was associated with longer RFS (cause-specific HR 0.80, 95% CI 0.67 to 0.96; p=0.016) and OS (HR 0.58, 95% CI 0.47 to 0.71; p<0.001). Per-protocol analyses were directionally consistent. CONCLUSION: Postoperative GLP-1RA initiation, compared with DPP-4i initiation, was associated with delayed recurrence and longer OS; prospective confirmation is warranted. TRIAL REGISTRATION NUMBER: ChiCTR2600118495.
Alnatsha A, Xu J, Habshi T
… +33 more, Li Q, Rickú K, Allawadhi P, Saka D, Dai R, Xue Y, Nguyen H, Stadler H, Weltermann T, Zhou Q, Schreiner N, Xue Y, Rittinghausen V, Ormanns S, Klauschen F, Zhang D, Böck S, Benoit M, Ben Khaled N, Lahiri S, Imhof A, Klingl A, Jaiswal A, Sahoo GP, Regel I, Mueller S, Öllinger R, Rad R, Belka C, Bange T, Lauber K, Mayerle J, Mahajan UM
BACKGROUND: As key constituents of cellular sphingolipid pools, sphingomyelin (SM) and ceramide (CER) are central to the regulation of cancer cell death and survival. The metabolic flux between these two lipids is a vita...BACKGROUND: As key constituents of cellular sphingolipid pools, sphingomyelin (SM) and ceramide (CER) are central to the regulation of cancer cell death and survival. The metabolic flux between these two lipids is a vital component of the cellular stress response, yet the underlying regulatory mechanisms in cancer remain elusive. Acid sphingomyelinase (SMPD1) facilitates the conversion of SM to CER, functioning as a key enzymatic driver of CER-mediated signalling. OBJECTIVES: Herein, we aim to evaluate the role of SMPD1-driven sphingolipid metabolism in pancreatic carcinogenesis. DESIGN: A targeted quantitative analysis of the plasma metabolome was conducted involving patients with pancreatic ductal adenocarcinoma (PDAC, n=202) and matched control subjects (n=204). Multiplex immunohistochemistry was performed on resected PDAC (n=122) to identify expression of SMPD1 with tumour and immune cell markers. CRISPR/Cas9 driven Smpd1-deleted murine cell lines were generated and subsequently assessed for their carcinogenic potential in vitro. The effects of deletion on tumour formation were evaluated using both syngeneic orthotopic and metastatic murine models. RESULTS: Here, we demonstrate that tumour cell-autonomous expression of SMPD1, in pancreatic ductal adenocarcinoma (PDAC), is associated with poorer patients' outcomes. ablation in murine PDAC cells resulted in reduced proliferation and migration in vitro and decreased metastases and tumour burden in vivo. Integrated transcriptomic, metabolomic and proteomic studies revealed that SMPD1 abrogation impairs Kras oncogenic signalling and, thus, reduces tumour burden. Reduced plasma membrane interaction of Kras was associated with SMPD1-dependent sphingolipid metabolism. Notably, the SMPD1 inhibitor (ARC39) potently synergised with the Kras inhibitor (MRTX1133). CONCLUSION: In summary, SMPD1 regulated plasma membrane sequestration of Kras represents a potential therapeutic target within the Kras signalling pathway for intractable PDAC.
Extraintestinal () infection rarely involves bone and can mimic malignancy. A man in his 70s with chronic kidney disease presented with a longstanding, painless, fluctuant anterior lower leg mass without systemic or gas...Extraintestinal () infection rarely involves bone and can mimic malignancy. A man in his 70s with chronic kidney disease presented with a longstanding, painless, fluctuant anterior lower leg mass without systemic or gastrointestinal symptoms. Imaging showed a proximal tibial lytic lesion and aspiration of a superficial collection grew Symptoms persisted despite 4 weeks of oral amoxicillin-clavulanate (875-125 mg every 12 hours) plus oral metronidazole (500 mg every 8 hours). MRI demonstrated chronic tibial osteomyelitis with cortical disruption and a contiguous intramedullary and soft tissue abscess consistent with a Brodie's abscess. He underwent excisional debridement with dead-space management and local vancomycin, followed by prolonged pathogen-directed antimicrobials. Two deep intraoperative cultures again yielded rare with negative aerobic and blood cultures. He improved without amputation and remained stable at 9-month follow-up.
PURPOSE: To evaluate the impact of socioeconomic factors on survival in patients with HCC undergoing interventional LRT at a tertiary center. MATERIALS AND METHODS: A retrospective cohort of 1,091 HCC patients treated wi...PURPOSE: To evaluate the impact of socioeconomic factors on survival in patients with HCC undergoing interventional LRT at a tertiary center. MATERIALS AND METHODS: A retrospective cohort of 1,091 HCC patients treated with interventional LRT (2000-2022). Clinical and socioeconomic data (gender, insurance, race, education, language, marital status) were collected. Survival analysis utilized Kaplan-Meier and multivariable Cox regression to assess the impact of socioeconomic factors . Among identified patients (median age: 63 [IQR=12.14], 81% male), the majority had Medicare (43%) or private insurance (33%), were White (63%), had a college (42%) or high school (45%) education, and were married (51%). Median AFP was 11 (IQR=76); most were Child-Pugh B (72%), BCLC Stage A (66%) and ECOG 0 (75%). Overall mortality was 62%, and 23% underwent liver transplant. RESULTS: Female gender (HR 1.26, 95% CI 1.03-1.55, p = 0.028), lower education (high school vs. college; HR 1.24, 95% CI 1.04-1.50, p = 0.015), and being divorced (HR 1.43, 95% CI 1.08-1.90, p = 0.012) were independently associated with increased mortality. Asian race predicted improved survival (HR 0.44, 95% CI 0.29-0.67, p < 0.05). CONCLUSION: Asian race, male gender, marriage, and higher education independently predicted better survival in HCC patients receiving interventional LRT.
Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and metabolic plasticity, limiting the efficacy of standard chemotherapy. Targeting metabolic vulnerabilities presents a promising strategy to...Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and metabolic plasticity, limiting the efficacy of standard chemotherapy. Targeting metabolic vulnerabilities presents a promising strategy to overcome chemoresistance. This study investigates the synergistic efficacy and underlying mechanisms of combining energy metabolism inhibitors with chemotherapeutic agents in MDA-MB-231, a representative TNBC cell line. Through cell viability screening, we identified two potent synergistic regimens: gemcitabine with metformin and 5-fluorouracil with 3-bromopyruvate. Real-time bioenergetic profiling demonstrated that these combinations significantly disrupted the energy metabolic phenotypes of these cells. To elucidate the molecular mechanisms, we employed Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight tandem Mass Spectrometry (UPLC-Q-TOF-MS/MS) metabolomics coupled with stable isotope-labeled metabolite quantification. Our data revealed that metabolic inhibition sensitized cells to chemotherapy by inducing profound reprogramming of amino acid and lipid metabolism, tightly linked to energy deprivation. Pathway analysis confirmed that the therapeutic efficacy relies on the specific modulation of amino acid pathways associated with central carbon metabolism. Collectively, this study provides a mechanistic rationale for integrating energy metabolism inhibitors with chemotherapy, offering novel therapeutic strategies to enhance clinical outcomes in TNBC.
Wang X, Dong W, Shen R
… +17 more, Yu X, Zhang Y, Wang W, Yin X, Hu Y, Peng X, Yang G, Rao Q, Deng X, Wang R, Tang F, Huang Y, Jin Z, Cai Q, Xu H, Tang Y, Du D
INTRODUCTION: The recent global outbreaks of monkeypox virus (MPXV) and chikungunya virus (CHIKV) underscore the urgent need for rapid, accessible, and cost-effective diagnostic methods. Conventional CRISPR/Cas fluoresce...INTRODUCTION: The recent global outbreaks of monkeypox virus (MPXV) and chikungunya virus (CHIKV) underscore the urgent need for rapid, accessible, and cost-effective diagnostic methods. Conventional CRISPR/Cas fluorescence assays rely on trans-cleavage of ssDNA/RNA reporters labeled with expensive fluorophores and quenchers, which limits widespread application. OBJECTIVES: This study aims to develop and optimize a label-free, fluorogenic DNA aptamer-based reporter for a portable, one-pot Cas12a detection system capable of highly sensitive detection of MPXV and CHIKV directly from clinical specimens. METHODS: We evaluated commonly used ssDNA aptamers for their fluorescence emission upon Thioflavin T (ThT) binding and their cleavage efficiency by Cas12a. Through systematic mutagenesis targeting G-rich regions, we enhanced fluorescence emission. Additionally, poly-A linkers were introduced between G-rich motifs to promote Cas12a cleavage efficiency. Circular dichroism (CD) spectroscopy confirmed G-quadruplex (G4) formation in the aptamers. The assay's sensitivity and specificity were assessed using simulated clinical samples, followed by validation with actual clinical specimens. The performance of direct detection from simulated clinical samples was compared to qRT-PCR. A battery-powered heating-pad, a mini-centrifuge, and a flashlight were used to validate its POCT applicability. RESULTS: We designed and optimized a cost-effective, stable fluorogenic ssDNA aptamer that specifically binds to ThT. The aptamer ThT-3-5.1 exhibited the highest fluorescence enhancement and cleavage efficiency by Cas12a. Leveraging this aptamer, we developed a rapid, portable, one-pot detection platform (ROD-ThT) capable of detecting as few as 1 copy/reaction of MPXV and CHIKV nucleic acids within 35 min. Validation with clinical samples confirmed the assay's reliability without the need for nucleic acid purification. CONCLUSION: Our simple, efficient, portable, and affordable ROD-ThT platform holds great promise for disease diagnostics and management, particularly in resource-limited settings.